The goal of this mid-career mentor award is to expand training in clinical virology, with focus on HSV-2 infections, at the University of Washington, through collaborations with several ongoing training programs. Dr. Wald is a successful and well-funded clinical investigator with a record of mentoring infectious disease fellows and graduate students. The proposed research is a continuation of two thematically related projects from Dr. Wald's ongoing research program. Both projects focus on populations that suffer disproportionably from HSV-2 infections: Pregnant women and HIV infected persons. The first project focuses on prevention of neonatal HSV. The specific aims are: 1) To evaluate the effect of HSV serologic testing of pregnant women alone versus pregnant women and their partners on sexual behavior in 3rd trimester of pregnancy;2) To evaluate the efficacy of acyclovir therapy in prevention of viral shedding at delivery among HSV-2 seropositive women and the effect of acyclovir administered during labor on the neonate;3) To develop and test a rapid PCR assay to detect genital HSV shedding among women at the time of labor. This approach to HSV prevention during pregnancy combines behavioral, pharmacologic, and novel diagnostic tools. The second project focuses on interactions between HSV-1 and HIV. The specific aims are: 1) To measure the effect of clinical and subclinical HSV-2 reactivation on mucosal HIV replication;2) To determine the effect of HSV-2 reactivation on systemic HIV replication in HIV-infected patients treated with HAART and not treated with HAART;3) To determine the effect of HAART on HSV reactivation in HIV infected persons. The program integrates epidemiologic, clinical and experimental approaches to understanding the pathogenesis, sequelae and prevention strategies for HSV-2 infection and aims to provide supervised research mentorship in patient-oriented clinical virology to trainees with a variety of backgrounds. These will include fellows in infectious diseases (internal medicine, pediatrics and ob-gyn), medical students and residents, and graduate students in epidemiology. The program is built on a successful clinical research infrastructure that includes clinical facilities, data management, data analysis and biostatistics, and close collaborations with lab-based scientist that allows for translational research. Training in ethics of conduct of research is also provided, as is access to seminars, collaborators and classes in related fields.